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Dangerous viruses: New weapons against new foes

Dangerous viruses: New weapons against new foes

Bombing near polio vaccine site in Pakistan

PESHAWAR, Pakistan —

At least two police officers were killed and a dozen people wounded on Monday when a bomb went off near a health care facility where polio vaccines were being dispensed outside this northwestern Pakistani city, officials said.

As the World Health Organization struggles to make polio the second disease (after smallpox) to become extinct in the wild, it confronts a morass of extremist politics that feeds on the fear of Western culture and influence.

But polio is hardly our only problem virus. Viruses, like people, can fly in a day from the furthest corners of the Earth to New York, Tokyo or Hamburg, and so we see more scary stories about “new” viruses:

Middle East Respiratory Syndrome, a relative of SARS, emerged in Saudi Arabia in 2012, and has killed 58 out of 138 people infected.

West Nile virus, first seen in Uganda in 1937, has spread to more of Africa, Asia, Australia, the Middle East, Europe and the Americas. The U.S. death toll in 2012 was a record: 286.

A highly lethal bird flu continues to infect birds, and occasionally people. If the virus evolves to spread directly from person to person, it could cause a worldwide epidemic.

People wear face masks during the outbreak of swine flu in Kobe, Japan, in 2009. Prevention is often the only option when a new virus “breaks out.”

The sooner a disease organism can be identified, the sooner quarantines, controls and countermeasures can begin.

Historically, epidemiologists have searched for viruses — like the larger disease-causing bacteria and parasites — after a pattern of infectious disease is noticed. Their studies look at the pathogen’s natural reservoirs, patients and the pathways that move a pathogen from one human to another. The 1953 book, Microbe Hunters1, is the classic description of epidemiological investigation.

But with the rising number of new viruses, is old-school fast enough?

Too many bugs in the woods

Diseases that move from non-human animals to people are called zoonotics, and the increasing number of people using advanced techniques to study disease helps explain the rise in viral zoonotics.

“Statistically, over the past few decades, we are seeing a real increase in the emergence of zoonotics,” primarily from wild animals, says Jon Epstein, associate vice president of conservation medicine at the non-profit EcoHealth Alliance. “This points to things changing on the planet, and those changes are largely human-driven: population expansion, agricultural expansion to forests or pristine habitat, urbanization, and global travel and trade. All the things we do as part of our dynamic growth process are forcing an increase in contact with wildlife, and with domestic animals, and that’s creating more opportunity for viruses to jump from one species to another.”

Although we are emphasizing viruses from wildlife, in Brazil, cattle are at the root of an outbreak of vaccinia virus — a relative of smallpox.

Every so often, skeptics may wonder if the threat of emerging virus has been hyped. As we hear warnings that the H5N1 virus is gaining the dangerous capacity to spread between humans, this strain of bird flu has yet to cause a pandemic.

But it’s chastening to remember that in 1917-18, the H1N1 influenza, also an avian flu virus, killed between 50 and 100 million (from a population of less than 2 billion).

New diseases are unpredictable, says Epstein. “Every emerging disease is like an earthquake. It’s infrequent but potentially catastrophic; and we don’t know in advance. We have to be prepared: HIV came from a chimpanzee, and it became the biggest infectious disease, global-health issue of our time.”

It’s not just the uncounted number of viruses infecting (though often not harming) the animals that share our planet. Increasing trade, travel and crowding of the animals’ natural habitat are exposing more people to these potential pathogens.

The traditional response to infection takes too long and costs too much, and in the meantime, people die. What to do?

Two new approaches to the emerging virus problem are based on a better understanding of the ecology of viral disease: speeding up detection, diagnosis and control; and designing prevention more broadly, to focus on the ecology of disease.

Christine Jost (right) works with Indonesian partner to control bird flu in Indonesia during 2006.

Pigs, bats and date-palm sap: The Nipah manifesto

In 1998, an unknown virus began to cause seizures and vomiting among workers at Malaysian pig farms. Neither vaccine nor specific treatment was available for what is now called Nipah virus; and the fatality rate reached 70 percent.

The symptoms resembled encephalitis, which is carried by mosquitoes, but insecticides failed to slow the outbreak, so the government ordered a million pigs destroyed.

Photo: Micah Hahn

Sap of the date palm is collected in this jug as a cheap, natural soda in Bangladesh.

Nipah disappeared from Malaysia but surfaced in Bangladesh in 2001. By then, fruit bats had been identified as the virus’s natural reservoir, “but nobody was sure how it got to people in a Muslim country with few pigs,” says Micah Hahn, who investigated the outbreak with the International Center for Diarrheal Disease in Bangladesh and is now at a Centers for Disease Control outpost in Fort Collins, Colo. “We did a case-control study, interviewed patients and others, used the tried-and-true techniques of outbreak investigation,” and eventually identified a totally different pathway.

The virus was contaminating sap of the date palm tree, a popular local drink. As Hahn describes it, “A climber would shave off part of the bark, insert a bamboo spout to collect the sap overnight, and people would drink it fresh, like a glass of sugar water.” But fruit bats, foraging at night, drank sap from the collection pots, and — how can we put this delicately? — poisoned it with their virus-rich urine or feces.

That explained the outbreak — but a question remained. If the bats were drinking sap in large parts of Bangladesh, “It did not make sense to find an isolated Nipah belt” with much higher prevalence of Nipah, says Hahn.

The answer turned out to reside in ecology. Outside the belt, the rural communities were smaller, and the forest was relatively intact and dominated by stands of teak.

Photo: Asaduzzaman Asad, Dec. 2011

It’s all hands on deck as (left to right) Shaike Faruk, Micah Hahn and Mohammad Wahid Ahmed gear up to sample bat roosts in Bangladesh.

The human population was denser inside the Nipah belt, where the forest was cut up by houses, rice paddies and fruit trees. “You could find 30 species in a backyard,” says Hahn. “For bats, it’s a smorgasbord, they love to live near populations because people have so many food sources.”

So environmental conditions explained the Nipah belt: “The landscape was creating an area that was fruitful for the bats, and there was a lot of opportunity for interactions among bats and people,” Hahn says.

Once the infection pathway was clear, a low-tech solution was introduced to the Nipah zone, Hahn says: Screens that excluded bats from the collection pots.

Virus hunting, updated

When a virus makes news, it’s usually bad news. So how great is the total threat? Helping answer that question is a goal of Predict, part of the Emerging Pandemic Threats program at the U.S. Agency for International Development.

The project is screening for new viruses in bats, rodents and primates, which all cause an inordinate burden of disease. “We will capture, sample, release and test, see what viruses they are carrying,” says Epstein. “It’s totally unprecedented, but it’s more than a group of Americans. There is a very strong effort to work with host-country governments, particularly wildlife departments, to establish capacity to do this kind of work.”

How many new viruses?

How many pathogenic viruses lurk in the wild? Simon Anthony, of EcoHealth Alliance and Columbia University, recently found 55 viruses in one species of bat. If that’s true of the other 5,485 mammal species, they harbor an estimated 320,000 viruses.

Indian Flying Fox flying over Tissamaharama, Sri Lanka. A new study found 55 types of virus in this bat; 50 were new to science.

Is this number reassuring or frightening? “To my mind, it’s a lot less than we thought it would be,” says co-author Peter Daszak. “I was expecting 10 million, or maybe 2 million.”

Daszak says a few hundred viruses are now discovered each year. “If we as a species decided this was worth doing, we maybe could do it [survey all mammals for viruses] in 10 years” at cost of a few hundred million dollars per year. (Although other species carry viruses, mammalian zoonotics tend to be more dangerous because we are genetically more like mammals.)

Predict has already found hundreds of viruses, “but the challenge is interpreting the results,” says Epstein. One obvious red flag is a molecular kinship to known pathogens, but at this point, “We don’t know if they cause disease or whether they have previously caused human or livestock disease.”

The Predict project is focusing on 20 countries that have been identified as “hotspots” for emerging viruses. “People said there is no way you can predict the next emerging disease, but I felt this was not true,” says Peter Daszak, president of EcoHealth Alliance, who helped develop the analysis. “There must be a common theme to emerging infectious diseases that could be analyzed to predict where the next ones will be come from.”

Daszak and colleagues analyzed 60 years of data on emerging diseases, corrected for the historic over-emphasis on where science was done (mainly in developed countries), and located hot spots in tropical countries with much biodiversity, and therefore many potential viral hosts.

Tony Goldberg, UW-Madison

A field team prepares to collect virus-discovery samples in Kibale National Park, Uganda. (Left to right: David Hyeroba, Geoffrey Weny, Tony Goldberg, Tony Kidega, Alex Tumukunde.)

But geography is only half the story. “What drives this is economic incentives, such as the push, here in the U.S., to have fruits and vegetables all year round shipped in from tropical countries,” says Daszak, who points out that cutting forest for farms exposes farm workers to the local viral zoo. “We are part of the problem, and we need to rethink the way we do things.”

Can we halt a virus we haven’t even detected?

One node of this rethinking — evident in the Nipah virus example — is an intensified focus on pathways — the routes that new viruses travel to their potential victims. To identify pathways, a group of Wisconsin researchers, funded by the joint National Science Foundation and National Institutes of Health Ecology and Evolution of Infectious Diseases Program, is “focusing on target populations with interesting ecologies,” says Tony Goldberg, principal investigator of the project.

“We are working in Kibale National Park in Uganda, an area with a pronounced human-wildlife interface, with a fragmented ecosystem in which people and primates interact frequently and often antagonistically,” Goldberg says. “Habitat loss is accelerating, the human population is growing, there’s a high prevalence of HIV in people, the monkeys are stressed ecologically, nutritionally, socially.”

Kibale and similar locations evince signs of what Goldberg calls “ecological overlap”:

Although the virus that gave rise to HIV apparently “jumped” from a primate to a hunter long ago, Goldberg says it’s critical to look at other transmission pathways. “We find examples of people who do not eat monkeys, but are bitten by monkeys if they share a common environment.”

In Bali, Goldberg says, temple monkeys “bite people often; it’s a transmission pathway defined by human culture. In Uganda, people smear corn in the field with cattle dung, hot pepper and sand, to keep monkeys from eating the crop.” That can lead to a three-way pathogen mixer: “The people are exposing themselves and the monkeys to cattle feces.”

Hope ahead?

If human behavior is so critical in the movement of viruses, Goldberg says social science may be “the next frontier. The viral biology is very interesting for a biologist, but most trends we see in emerging infectious disease are traceable to human changes in the world. Ultimately the people who are going to solve this are the social scientists.”

“We have two choices,” says Goldberg. “We can sit in the living room and wait for the next new virus, and then try to design a vaccine, diagnostics, and a quarantine program. We have the technology to do these, but it’s slow and expensive.”

Mass polio vaccination in Columbus, Georgia, during the National Polio Immunization Program, circa 1960. Traditionally, we design vaccines when a new disease arises, then and promote them among the public, just as we did to curb poliomyelitis. But scientists are exploring ways to block transmission before an epidemic starts.

To those who favor the ecological approach, Goldberg says, “Our central hope is not only about virus discovery. There are certain key ecological pathways in nature that facilitate the movement of all sorts of pathogens. If we can identify those pathways, ultimately it boils down to prevention. We can block transmission whether we know the identity of the viruses or not.”